title: Acute effects of single-dose olanzapine on metabolic, endocrine, and inflammatory markers in healthy controls.
abstract: Atypical antipsychotics may "directly" influence glucose homeostasis, increasing risk of type 2 diabetes independently of changes in adiposity. Animal models suggest direct effects after even a single dose of certain atypical antipsychotics on glucose dysregulation. Here, we investigated effects of a single-dose olanzapine (OLA) on glucose metabolism in healthy volunteers, thereby minimizing confounding effects of the illness of schizophrenia and adiposity. In a randomized double-blind crossover design, 15 subjects were administered 10 mg of OLA or placebo at 7:00 A.M. on separate study dates. A frequently sampled intravenous glucose tolerance test was initiated 4.25 hours later to assess changes in glucose homeostasis, including an index of insulin sensitivity, disposition index, glucose effectiveness, and acute insulin response to glucose. We also examined effects on cortisol, prolactin, fasting free fatty acids (FFAs), insulin-mediated suppression of FFAs, and adipocytokines (leptin, adiponectin, C-reactive protein, interleukin 6, and tumor necrosis factor α). Complete data for both visits were analyzed for 12 subjects. Olanzapine treatment significantly decreased glucose effectiveness (P = 0.041) and raised fasting glucose over 4.25 hours (P = 0.03) as compared to placebo. Olanzapine was associated with lower serum cortisol (P = 0.003), lower fasting FFA (P = 0.042), and increased prolactin levels (P < 0.0001). We therefore suggest that a single dose of OLA may invoke early changes in some parameters of glucose and lipid metabolism, as well as endocrine indices.
authors.affiliation: From the *Center for Addiction and Mental Health; †Institute of Medical Sciences; ‡Department of Nutritional Sciences, University of Toronto; §Department of Medicine, St. Michael's Hospital; ∥Department of Physiology; ¶Department of Psychology; #Department of Psychiatry, University of Toronto; **University Health Network; and ††Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Margaret Karolina
authors.initials: MK
authors.lastname: Hahn
authors.forename: Tom M S
authors.initials: TM
authors.lastname: Wolever
authors.forename: Tamara
authors.initials: T
authors.lastname: Arenovich
authors.forename: Celine
authors.initials: C
authors.lastname: Teo
authors.forename: Adria
authors.initials: A
authors.lastname: Giacca
authors.forename: Valerie
authors.initials: V
authors.lastname: Powell
authors.forename: Leigh
authors.initials: L
authors.lastname: Clarke
authors.forename: Paul
authors.initials: P
authors.lastname: Fletcher
authors.forename: Tony
authors.initials: T
authors.lastname: Cohn
authors.forename: Roger S
authors.initials: RS
authors.lastname: McIntyre
authors.forename: Sylvia
authors.initials: S
authors.lastname: Gomes
authors.forename: Araba
authors.initials: A
authors.lastname: Chintoh
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Remington
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D000077152:Olanzapine; D011388:Prolactin / Q000378:metabolism
chemical_list: D054392:Adipokines; D014150:Antipsychotic Agents; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D001569:Benzodiazepines; D011388:Prolactin; D000077152:Olanzapine; D006854:Hydrocortisone